Molecular characterization of a new recombination of the SIL/TAL‐1 locus in a child with T‐cell acute lymphoblastic leukaemia

Abstract

Summary. Deletions involving the SIL-TAL-1 locus are seen in 15% of T-acute lymphoblastic leukaemias (T-ALL). To date, seven deletions have been described, spreading over 90 kb of chromosome 1, fusing SIL to the TAL-1 gene and resulting in over expression of TAL-1. During the diagnostic screening of the TAL-1 deletion in 176 T-ALL patients, we identified one case showing a new SIL rearrangement. A novel fusion transcript was identified between the SIL exon 1a and an unknown sequence (633-cDNA). Polymerase chain reaction (PCR) screening of a human cDNA library confirmed the existence of this transcript. Using long-distance PCR on patient DNA, we obtained a genomic fragment containing SIL exon 1b, a portion of intron 1b, an unknown sequence and the 633 sequence. Using DNA from healthy donors, a partial genomic map of 633-DNA was found to be identical to the restriction map of the PCR fragment amplified from patient DNA. To define the chromosomal origin of 633-DNA, a YAC human genomic library was screened. Two clones containing 633-DNA were found, mapping to chromosomal region 1p32 and both contained SIL and TAL-1 sequences. By searching GenBank, we identified PAC RP1-18D14 which contains SIL, TAL-1 and 633-DNA, confirming this novel rearrangement as a new deletion of the SIL/TAL-1 locus.

Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951

“…However, if we make a compilation of results obtained in studies gathering more than 70 patients, including ours, we obtain a mean estimation of only 17% for SIL-TAL frequency in childhood T-ALL, suggesting this frequency has probably been overestimated in the past. 6,[36][37][38][39] A possible explanation is that, as shown in our and other studies, patients positive for SIL-TAL usually display a high WBC count and could be preferentially selected in retrospective studies, depending on the availability of stored material. The regular increase in SIL-TAL frequency with age that we observed is surprising because this defect is rarely seen in adult malignancies.…”

V(D)J Recombinase-Mediated Processing of Coding Junctions at Cryptic Recombination Signal Sequences in Peripheral T Cells during Human Development

“…The RIC scores indicate that the conserved 5Ј cRSS site can be used as both a 12-RSS and 23-RSS. Of clinical importance is that RAG-mediated deletions at the HPRT locus are analogous to sil-tal1 deletions observed in 15-26% of T cell acute lymphoblastic leukemias (27,46,47). RAG-mediated rearrangements at the sil-tal1 loci result in a ϳ90-kb deletion altering the expression of the TAL1 transcription factor.…”

Clinical features and outcome of SIL/TAL1-positive T-cell acute lymphoblastic leukemia in children and adolescents: a 10-year experience of the AIEOP group

“…This study, like many others aimed at assessing the role of single genetic lesions, was not able to detect a prognostic value in childhood T-ALL, suggesting that further investigations should take into account multiple genetic alterations rather than focus on single ones. Antonella Colombini, 3 Nicola Santoro, 5 Stefania Varotto, 6 Maurizio Caniglia, 7 Daniela Silvestri, 2,3 Caterina Consarino, 8 Laura Levati, 9 Elisa Magrin, 6 Franco Locatelli,…”

“…The SIL/TAL1 fusion product gives rise to the inappropriate expression of TAL1, which, in turn, may promote T-cell leukemogenesis. 1,[6][7][8] The clinical relevance and the prognostic value of this rearrangement remain unclear.…”

“…7 Since SIL/TAL1 type 2 deletion is quite rare, the 69 SIL/TAL1 type 1 negative patients who were not screened for type 2 deletion were included in the negative cohort. Thus a total of 56 cases (16%) were positive for SIL/TAL1.…”